Laboratory Features of Cutaneous Lupus Erythematosus 313

CHAPTER 23 Laboratory Features 23 of Cutaneous Lupus Erythematosus Shuntaro Shinada, Daniel J. Wallace Assuming that patients with cutaneous lupus erythematosus (CLE) do not fulfill the American College of Rheumatology criteria for systemic LE (SLE) (Tan et al. 1982), what laboratory features should the clinician look for? Interestingly, there are several. This chapter attempts to elucidate the laboratory abnormalities associated with CLE, the most common being hematologic (anemia and leukopenia), erythrocyte sedi- mentation rate (ESR), antinuclear antibodies (ANAs), and antiphospholipid antibodies. These features are compared with those observed in SLE and certain cutaneous clinical subsets that have been studied. General Approach to Laboratory Testing When a dermatologist, family practitioner, internist, or rheumatologist first sees a patient with CLE, their principal concern should be to rule out evidence of systemic disease. After all, 15% of patients with CLE progress to SLE in 10–15 years of obser- vation (Rowell 1984). In addition to a complete medical history and physical examination, clinical laboratory findings can be very helpful in this regard. Specifically, a blood chemistry panel allows screening for renal or hepatic involvement. Creatine phosphokinase testing assists in ruling out muscle inflammation. Evidence for autoimmune hemolytic anemia or thrombocytopenia is looked for in the complete blood cell count as well as in the lactic dehydrogenase, reticulocyte count, Coombs’ direct antibody testing, serum haptoglobin, and antiplatelet antibodies. A routine urinalysis free of cellular casts or protein makes it highly unlikely that the kidney is involved. Specific autoantibodies, almost never observed in CLE, if found, can suggest central nervous system disease (antiribosomal P,antineuronal), mixed connective tis- sue disease (anti-RNP), or other disease subsets. In our practice, all patients have annual chest radiographs and electrocardiograms, since there are no blood tests to screen for cardiac or pulmonary involvement. Finally, additional imaging or electri- cal tests (electromyography, nerve conduction studies, 2-D echocardiography with Doppler) are occasionally ordered, and the results should be normal in CLE. If not, muscle, nerve, cardiac, or pulmonary disease representing visceral involvement should be ruled out. This chapter assumes that the presence of systemic disease is not under consider- ation. The question remains, are there any laboratory tests worth ordering to monitor or better characterize CLE? 312 Shuntaro Shinada, Daniel J. Wallace Medications Used to Manage Cutaneous Lupus Erythematosus Warrant Periodic Laboratory Monitoring Although the different therapeutic options for CLE are discussed in later chapters, it is valuable to note the laboratory abnormalities associated with the medications used to treat CLE (Table 23.1). Table 23.1. Laboratory abnormalities associated with use of drugs for cutaneous lupus erythematosus Medication Laboratory side effects Laboratory monitoring Antimalarials Monitor CBC, serum creatinine, Chloroquine Hemolysis secondary to and LFT every 2 months G-6-PD deficiency, decreased creatinine clearance Hydroxychloroquine Decreased creatinine clearance, decreased cholesterol profile, agranulocytosis (rare) Quinacrine Aplastic anemia Antileprosy drugs Dapsone Sulfhemoglobinemia, methe- Monitor baseline G-6-PD levels. moglobinemia, hemolysis Monitor CBC every 2 weeks for the secondary to G-6-PD defi- first 3 months, then every 2 months ciency, hepatotoxicity thereafter Monitor baseline LFTs then every 2 months thereafter Thalidomide Highly teratogenic, neutro- Baseline pregnancy test, then penia weekly for the first month, then monthly thereafter Monitor CBC every 2 months Methotrexate Blood dyscrasias, hepato- Monitor baseline LFTs, CBC, serum toxicity creatinine, then weekly until dose stabilized, then every 1–2 months thereafter Cyclosporine Increased serum creatinine Monitor 2 baseline creatinines, then level every 2 weeks for the first 3 months, then every month thereafter Azathioprine Thrombocytopenia, neutro- Monitor baseline CBC, LFTs, then penia, hepatotoxicity every 2 weeks for the first month, then every 1–3 months thereafter Glucocorticosteroids Increased serum glucose Monitor baseline lipid panel, CBC, level; increased VLDL-C, serum glucose and potassium, then HDL-C, and TG levels monitor serum/urine glucose every 3–6 months CBC, complete blood cell count; G-6-PD, glucose-6-phosphate dehydrogenase; HDL-C, high- density lipoprotein cholesterol; LFTs, liver function tests; TG, triglyceride; VLDL-C, very-low- density lipoprotein cholesterol. Laboratory Features of Cutaneous Lupus Erythematosus 313 Antimalarials The three antimalarials available at this time for the treatment of CLE are chloroquine, hydroxychloroquine, and quinacrine. Overall, these drugs are relatively safe, but there are some laboratory abnormalities to consider. Chloroquine slightly decreases creatinine levels in half of its users, most likely by raising plasma aldosterone levels (Musa- bayane 1994).Forty-five percent of hydroxychloroquine is excreted in the kidneys,and the drug is associated with up to a 10% decrease in creatinine clearance (Landewe et al.1995).Therefore,the dosage should be adjusted for patients with renal impariment. Antimalarials also have a beneficial antihyperlipidemic effect. Hydroxychloroquine induces a 15%–20% decrease in total cholesterol,triglyceride,and LDL levels (Wallace et al. 1990). It is associated with only one case of agranulocytosis, in a patient who was given 1,200 mg daily,which is up to six times the current recommended dosage (Polano et al. 1965), and a handful of case reports of various blood dyscrasias, such as aplastic anemia, leukopenia, thrombocytopenia, and hemolysis in individuals with glucose-6- phosphate dehydrogenase (G-6-PD) deficiency. Chloroquine has been implicated in rare reports of G-6-PD deficiency hemolysis (Choudhry et al.1978) and with agranulocytosis (Kersly and Palin 1959).Since chloroquine is known to concentrate in the liver, it should be used with caution in patients with hepatic disease or alcoholism or in conjunction with known hepatotoxic drugs. The prevalence of aplastic anemia among US soldiers in the Pacific during World War II rose from 0.66 to 2.84 per 100,000 after quinacrine’s introduction (Custer 1946). This represented 58 patients, 48 of whom received quinacrine. Of these, 16 were associated with overdoses, and two received marrow-suppressant drugs concurrently (Wallace 1989). It is therefore recommended that patients receiving antimalarial treatment have a complete blood cell count and a serum creatinine test every few months during therapy. Patients taking chloroquine or hydroxychloroquine should undergo ophthalmologic examination at 6- or 12-month intervals, respectively. Antileprosy Drugs Dapsone Dapsone’s use is limited by its toxic effects, which include sulfhemoglobinemia and methemoglobinemia, a dose-related hemolytic anemia, a “dapsone hypersensitivity syndrome,” and aplastic anemia (Meyerson and Cohen 1994, Mok et al. 1998). All patients treated with dapsone should have their baseline G-6-PD level checked. The drug should not be given to patients with low levels. Complete blood cell counts should be checked every 2 weeks for the first 3 months, then every 2 months thereafter. Toxic hepatitis and cholestatic jaundice have been reported early in therapy. Hyperbilirubinemia may occur more often in G-6-PD-deficient patients. Baseline and subsequent monitoring of liver function is recommended. Thalidomide Thalidomide is a highly teratogenic drug with antileprosy and antilupus effects via various mechanisms.Side effects include teratogenicity,fatigue,dizziness,weight gain, constipation, amenorrhea, dry mouth, and a non-dose-related polyneuropathy that is associated with chronic administration (Ludolph and Matz 1982). Because thalido- 314 Shuntaro Shinada, Daniel J. Wallace mide is so highly teratogenic,women of childbearing potential should have pregnancy testing. The test should be performed within 24 h of beginning thalidomide therapy and at regular intervals when appropriate.Pregnancy testing should also be performed if a patient misses her period or if there is any abnormality in menstrual bleeding. Decreased white blood cell counts, including neutropenia, have been infrequently reported in association with the clinical use of thalidomide. White blood cell count and differential should be monitored on an ongoing basis, especially in patients who may be more prone to neutropenia. Higher doses of thalidomide may predispose patients to coagulopathies. Methotrexate Although serious and sometimes fatal blood dyscrasias are a well-known conse- quence of high-dose methotrexate therapy, the Committee on Safety of Medicines in the United Kingdom (Dodd et al. 1985) stated in September 1997 that it was also aware of 83 reports of blood dyscrasias associated with low-dose methotrexate used to treat psoriasis or rheumatoid arthritis; there were 36 fatalities. Megaloblastic anaemia, usually with marked macrocytosis, has been reported in mainly elderly patients receiving long-term weekly methotrexate therapy (Dahl 1984). Methotrexate has been associated with periportal fibrosis and cirrhosis (Neu- berger 1995), and its potential for hepatotoxicity has been a source of some concern given its use in nonmalignant disorders such as psoriasis and rheumatoid arthritis. It is recommended that liver function

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